Study demonstrates link between appetite and elderly mortality

BEER-SHEVA, ISRAEL, 13 may 2009 – A new study by a Ben-Gurion University of the Negev (BGU) researcher reveals a linkage between elderly people's appetite and mortality rates, with those who report impaired appetite more likely to die sooner.

The study, published in the May issue of the Journal of Nutrition, Health & Aging, demonstrated a link between the Daily Activity Energy Expenditure (DAEE-- an accurate measurement of total physical activity), appetite and mortality among well functioning community-dwelling adults. Information on an elderly patient's eating habits may be important for health providers regarding risk for patient deterioration and mortality.

"These findings are important because they show how subjective appetite measurement can predict death, even when adjusting for health and many other variables," said Dr. Danit Shahar, a researcher with BGU's S. Daniel Abraham International Center for Health and Nutrition and Department of Epidemiology. "Past studies failed to show an association with survival. It was thought that decreased appetite may be an indicator or a result to other health problems, and that malnutrition, rather than low appetite was associated with mortality."

"Dietary Factors in Relation to Daily Activity Energy Expenditure and Mortality among Older Adults" analyzes data from the Health, Aging and Body Composition (Health ABC) study to demonstrate that higher DAEE is strongly associated with increased appetite, resulting in lower risk of mortality in healthy older adults. Using 298 older participants (ages 70-82 years) in the Health ABC study, researchers analyzed DAEE and dietary factors, including self-reported appetite, enjoyment of eating and intake assessed by the Block Food Frequency Questionnaire (FFQ) and Healthy Eating Index (HEI).

Participants who reported improved appetite were at lower risk for mortality. Similarly, participants who reported good appetite at baseline had a low risk for mortality. The results remained significant taking into account health status, physical activity, demographic and nutritional indices. Follow up was nine years.

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Shahar, D.R., B. Yu, D.K. Houston, S.B. Kritchevsky, J.-S. Lee, S.M. Rubin, D.E. Sellmeyer, F.A. Tylavsky, and T.B. Harris. "Dietary Factors in Relation to Daily Activity Energy Expenditure and Mortality among Older Adults." The Journal of Nutrition Health & Aging. May 2009; 13(5): 414-20.

Equality of the sexes? Not always when it comes to biology

MUHC researchers demonstrate that estrogen renders the innate immune system of women more powerful than that of men

Montreal, 13 may 2009– When it comes to immunity, men may not have been dealt an equal hand. The latest study by Dr. Maya Saleh, of the Research Institute of the McGill University Health Centre and McGill University, shows that women have a more powerful immune system than men. In fact, the production of estrogen by females could have a beneficial effect on the innate inflammatory response against bacterial pathogens. These surprising results were published today in the Proceedings of the National Academy of Sciences.

More specifically, estrogen naturally produced in women seems to block the production of an enzyme called Caspase-12, which itself blocks the inflammatory process. The presence of estrogen would therefore have a beneficial effect on innate immunity, which represents the body's first line of defence against pathogenic organisms. "These results demonstrate that women have a more powerful inflammatory response than men," said Dr. Saleh.

This study was conducted on mice that lack the Caspase-12 gene, meaning that the mice were extremely resistant to infection. The human Caspase-12 gene was implanted in a group of male and female mice, yet only the males became more prone to infection. "We were very surprised by these results, and we determined that the estrogen produced by the female mice blocked the expression of the human Caspase-12 gene," explained Dr. Saleh. "We were also able to locate where the estrogen receptor binds on the gene in order to block its expression, which indicates that the hormone exerts direct action in this case."

Since these experiments were conducted using a human gene, the researchers consider these results to be applicable to humans. This feature of the female innate immune system might have evolved to better protect women's reproductive role.

The positive effect of natural estrogen on our resistence to infection is also exhibited with synthetic hormones such as 17-beta-estradiol. This finding might therefore open the door to new therapeutic applications that reinforce the immune system, but a question remains: will men be amenable to the idea of being treated with an exclusively female hormone?

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Funding

This study was supported by grants from the Canadian Institutes for Health research and the Canadian Foundation for Innovation.

Dr Maya Saleh

Dr. Maya Saleh is a researcher with the Critical Care Division and the Centre for the Study of Host Resistance at the Research Institute of the McGill University Health Centre (MUHC) as well as an assistant professor with McGill University's Faculty of Medicine.

Research says older people need more sun

Spending more time in the sunshine could help older people to reduce their risk of developing heart disease and diabetes.

13 may 2009--Exposure to sunlight stimulates vitamin D in the skin and older people are more likely to have a vitamin D deficiency due to the natural aging process and changes in lifestyle.

Researchers at the University of Warwick have shown vitamin D deficiency is significantly associated with metabolic syndrome, a combination of medical and metabolic disorders that increase the risk of developing cardiovascular disease and diabetes.

The research team, led by Dr Oscar Franco at Warwick Medical School, investigated the association between vitamin D levels in the blood and the prevalence of metabolic syndrome in 3,262 people aged 50-70 years old in China.

His team found a high correlation between low vitamin D levels and the prevalence of metabolic syndrome. They found 94% of people in the study had a vitamin D (25-hydroxyvitamin D) deficiency or insufficiency. The results showed 42.3% of these people also had metabolic syndrome.

The results of the study, published in Diabetes Care journal, are consistent with the findings of other studies in Western populations and Dr Franco suggests vitamin D deficiency could become a global health problem.

He said: "Vitamin D deficiency is becoming a condition that is causing a large burden of disease across the globe with particular deleterious impact among the elderly. Our results are consistent with those found in British and American populations. We found that low vitamin D levels were associated with an increased risk of having metabolic syndrome, and was also significantly associated with increased insulin resistance."

Dr Franco said there were many factors which could explain why older people had less vitamin D in their blood, including changes in lifestyle factors such as clothing and outdoor activity.

He added: "As we get older our skin is less efficient at forming vitamin D and our diet may also become less varied, with a lower natural vitamin D content. Most importantly, however, the dermal production of vitamin D following a standard exposure to UVB light decreases with age because of atrophic skin changes. When we are older we may need to spend more time outdoors to stimulate the same levels of vitamin D we had when we were younger."

Vitamin D deficiency exists when the concentration of 25-hydroxy-vitamin D (25-OH-D) in the blood serum occurs at 12ng/ml (nanograms/millilitre) or less. The normal concentration of 25-hydroxy-vitamin D in the blood serum is 25-50ng/ml.

This study was carried out in collaboration with colleagues from the Shanghai Institute of Biological Sciences in China. The team recruited 3,262 community residents aged 50-70 from Beijing and Shanghai in China as part of the Nutrition and Health of Aging Population in China (NHAPC) project.

Dr Franco added: "Vitamin D deficiency is now recognised as a worldwide concern and metabolic syndrome has become a global epidemic. More research is needed to find out why older people are more likely to have lower levels of vitamin D and how this is linked to the development of metabolic syndrome and related metabolic diseases."

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Notes to editors

For further information please contact:

Peter Dunn, Press and MediaRealatiins Manager, University of Warwick,

A stronger backbone: DHEA hormone replacement increases bone density in older women

Drug combination could lower risk of fracture by 30 to 50 percent in women, according to Saint Louis University research

ST. LOUIS, 13 may 2009 – Taking a DHEA supplement combined with vitamin D and calcium can significantly improve spinal bone density in older women, according to a new study from a Saint Louis University scientist and his colleagues at Washington University.

"The results of our study are very promising. Similar studies have demonstrated much smaller benefits for bone than we found. However, calcium and vitamin D deficiencies, which are present in half of older adults, may have prevented DHEA from improving bone density in the earlier studies," said Edward Weiss, Ph.D., associate professor of nutrition and dietetics at Saint Louis University's Doisy College of Health Sciences and lead author of the study.

"In our study, we supplemented all participants with calcium and vitamin D to ensure that deficiencies were not present. This may explain why our study showed more favorable effects on bone density."

DHEA (dehydroepiandrosterone), a naturally occurring steroid hormone produced in the adrenal gland, gonads and brain, decreases with age. According to Weiss, low DHEA concentration has been associated with low bone density, which lead researchers to question whether restoring DHEA levels could improve or preserve bone health.

The two-year study divided men and women, ages 65 to 75 years old, into two groups. The first group received the DHEA supplement, vitamin D and calcium for two years. The control group received a placebo, vitamin D and calcium for the first year and then received the DHEA supplement the second year in place of the placebo.

The effects of the treatment differed for men and women. After the first year, women in the test group experienced an approximate 2 percent increase in bone density, while women in the control group did not see an increase. After the second year when both groups took the DHEA supplement, women in the test group experienced an additional 2 percent increase for a total of approximately 4 percent, while women who switched from placebo to DHEA also experienced an approximate 2 percent increase.

The same treatment, however, did not offer similar benefits for older men. Instead, men in both the test and control groups experienced a 1 to 2 percent increase in spinal bone density. According to researchers, the results suggest that vitamin D and calcium supplements, which were give to both groups, could be responsible for the increase in bone density.

The results of the study are promising for older women. According to Weiss, patients who achieve similar increases of 2 to 4 percent in spinal bone density with the help of medication experience a 30 to 50 percent reduction in risk of spine fractures.

Further, researchers say that the increase in spinal bone density experienced by women in the test group who took DHEA for two years, is at least as effective as other current therapies including estrogen and bisphosphonates, a class of prescription drugs that increases bone density.

However, like other therapies, the benefits of DHEA supplements were limited to spinal bone density. Neither men nor women experienced an improvement in hip bone density. Weiss says the hip may respond more slowly to bone-enhancing therapies than the spine, thus requiring more time to see a beneficial effect. More research is needed though.

"In addition to its beneficial effects on bone, DHEA replacement may have other benefits including improvements in risk factors for diabetes and heart disease, improvements in immune function, and improvements in psychological health," Weiss said.

While the research findings are promising, Weiss says that people should consult with their doctor before taking DHEA, which is an over-the-counter dietary supplement.

"Although DHEA is generally considered safe for consumption at 50 mg per day, it increases estrogen and testosterone levels which in turn could increase cancer risk," Weiss explained. "Therefore, DHEA supplementation should be avoided in men and women who have had cancer or who have a strong family history of cancer until further research can establish whether or not it is safe for these individuals."

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The study was funded with grants from the NIH, NIH General Clinical Research Center and NIH Clinical Nutrition Research Unit. Findings were published in the May 2009 issue of the American Journal of Clinical Nutrition.

Less than 1 in 5 heart problems are diagnosed before symptoms appear

Clinicians are missing golden opportunities to identify heart disease before patients start displaying symptoms, according to a study of 13,877 people published in the May issue of UK-based IJCP, the International Journal of Clinical Practice.

12 may 2009--Researchers from Oregon, Maryland and Delaware, USA, found that just over 11% of the respondents had been diagnosed with heart disease. However, only 19% of those individuals - who had been involved in the ongoing study for two years - said that their heart disease was picked up during routine screening.

More than half of the diabetic patients with heart disease who took part in the study (54%) reported that their heart disease was diagnosed when they became symptomatic and a further 22% said it was picked up while they were being treated for other health issues.

The figures were lower for individuals without diabetes. Just under half (48%) were diagnosed with heart disease when they became symptomatic and 15% were picked up during treatment for other conditions.

"Our study showed that not enough patients with heart disease are being picked up during routine screening or treatment for conditions like diabetes, which are commonly associated with heart problems" says lead author Dr Sandra J Lewis from the Northwest Cardiovascular Institute in Portland, Oregon. "The majority of those who took part in the study were not diagnosed until they started displaying symptoms."

Coronary heart disease (CHD) is the leading cause of death in the United States, accounting for more than 450,000 deaths a year. Approximately 15.8 million Americans who are 20 or older suffer from the disease.

"Many individuals do not show symptoms and go undiagnosed until the disease is in an advanced state, often when they have actually had a heart attack" explains Dr Lewis.

"That is why it is so important to diagnose CHD before patients experience their first crisis, by looking at major risk factors such as smoking, having high blood cholesterol, having high blood pressure, being overweight, being physically inactive or just getting older.

"Guidelines recommend that all adults over the age of 20 should receive risk factor screening from their family doctor every two to five years. There are more specific guidelines for patients with type 2 diabetes as their risk of a heart attack is twice as high as the general population."

The analysis from the SHIELD study (Study to Help Improve Early evaluation and management of risk factor Leading to Diabetes) was performed to see if ongoing recommendations for improved screening in the USA were resulting in more patients being diagnosed with heart disease before they became symptomatic.

It forms part of the larger SHIELD survey of 211,097 US households who responded to a national questionnaire.

More than 18,400 people who had participated in the baseline and first follow-up SHIELD surveys - and had diabetes or one of the five cardiometabolic risk factors - were sent questionnaires and 13,877 (75%) responded. Of these, 1,573 (11% of the total) had been diagnosed with heart disease.

Just under two-thirds had heart disease on its own (62%). They were predominantly male (59%) and white (91%) with an average age of 67. The remaining 38% had heart disease and type 2 diabetes. They were slightly more likely to be women (50.7%), 88% were white and their average age was 69.

The average time since diagnosis was 11.7 years in CHD patients without diabetes and 10.7 years in individuals with diabetes and CHD. Almost a third of the non diabetes group (31%) and 36% of the diabetes group had been diagnosed since 2001 when a number of consensus statements and guidelines on screening and prevention were published.

"Despite increased knowledge and awareness of the risk factors for CHD, many individuals are not diagnosed with heart disease until they are symptomatic" concludes co-author Dr Kathleen Fox from Strategic Healthcare Solutions in Monkton, Maryland.

"The fact that only a small percentage of the SHIELD respondents were diagnosed through screening indicates that there is a missed opportunity to diagnose heart disease during earlier, less severe stages of the disease.

"As blood pressure and weight are evaluated when most patients visit their family doctor, medical providers already have information about two key modifiable risk factors.

"Our study demonstrates the need for improved targeted education aimed at both patients and doctors to reduce heart disease before symptoms occur."

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The paper can be viewed free at: www.ijcp.org

More Cancer Tests Mean More False-Positive Results

12 may 2009-- The more cancer screening tests you undergo, the higher your risk of having at least one false-positive result, researchers say.

While that conclusion may seem like common sense, it's not something that patients or doctors often consider, suggest the authors of a study in the May/June issue of the Annals of Family Medicine.

False-positive results from routine cancer screening can cause undue worry and in some cases lead to unnecessary biopsies or treatments, experts note.

In the new study, "after 14 tests total, over half of the people in our study had a false-positive result. No test is perfect, and you would expect to see it go up over time, but how rapidly the risk went up was surprising," said the study's lead author, Dr. Jennifer Croswell, acting director of the office of medical applications of research at the U.S. National Institutes of Health in Bethesda, Md.

"It's important to know ahead of time the risk of false-positives," she said. "Screenings have to be thought of like any other medical intervention and it's important to have the discussion about the risks and the benefits."

Croswell and her colleagues reviewed data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which included nearly 70,000 participants. The study volunteers were between the ages of 55 and 74, and were randomly selected to receive either normal care or more intensive screening.

Those in the normal-care group were offered screening through their own private physicians as usual. Those in the intervention group were offered a baseline chest X-ray along with a yearly follow-up for two years for non-smokers and three years for smokers to check for lung cancer; a baseline flexible sigmoidoscopy to check for colorectal cancer, along with a three- or five-year follow-up; annual tests for cancer antigen 125 (CA-125) and a transvaginal ultrasound yearly to check for ovarian cancer in women; and an annual digital rectal exam to check for prostate cancer in men, as well as a prostate-specific antigen test.

No information was included on mammography for women in either the intervention group or the usual care group.

For those who had 14 screening tests during the study period, the cumulative risk of having at least one false-positive was 60.4 percent for men and about 49 percent for women. The cumulative risk of having to undergo an invasive diagnostic procedure due to a false-positive test result was almost 29 percent for men and just over 22 percent for women.

Croswell said the researchers weren't sure why the false-positive rate was higher for men, but it likely had something to do with the tests that were studied.

"The fact is that screening tests aren't diagnostic," said Robert Smith, director of cancer screening for the American Cancer Society. "A certain risk of false positives and false negatives are to be expected. You can try to very aggressively reduce the false-positive rate, but then you also cut into cancer detection rates," he explained.

"Most people place a higher priority on finding cancer early than preventing false-positives. I think the public often understands that false-positives happen," said Smith. But, he added, "We really need to do a better job of explaining to adults that there is a plus side and a down side to screening. We need to do a better job of letting people know what to expect, and that screening tests aren't perfect."

In another study in the same issue of the journal, researchers at the University of Auckland, New Zealand, take a different look at medical errors, and focus on the types of errors that patients make. While the study didn't attempt to rank which medical errors patients are most likely to make, the researchers did try to identify the types of errors patients might make.

They found that patient errors could be classified into two broad categories: action or mental errors. Action errors are related to patient behavior and may include coming late to an appointment or not following directions when taking medications. Mental errors are when a patient has compromised thought processes, memory problems or knowledge deficits. Examples of mental errors include forgetting to take medications or a failure to understand the doctor's instructions. The authors suggest that future research should try to account for these errors and find ways for clinicians and patients to work together to reduce errors.

Had a stroke? The elderly may not know, or remember

CHICAGO,22 may 2009– Older adults often do not realize or may even forget they have had a stroke and may not be a reliable source of medical information, U.S. researchers said on Monday.

Brain scans showed that while just 12 percent of seniors asked about strokes remembered having had one, nearly a third had brain damage showing they had.

The stroke itself could damage memory, and many people may also have so-called silent strokes that are never diagnosed at the time, Dr. Christiane Reitz of Columbia University Medical Center in New York and colleagues wrote in the Archives of Neurology.

"Stroke is associated with motor impairment but can also be accompanied by impairments in memory, sensation and speech or language, diminishing the ability of an individual to accurately report a history of stroke," they wrote.

The team studied magnetic resonance imaging or MRI scans of 717 people 65 or older who were covered by the federal Medicare insurance program for the elderly. "Approximately 75 percent of strokes occur in persons older than 65 years," the researchers wrote.

The volunteers were interviewed about their health and took some basic neurological and psychological tests. Patients and their caregivers also completed a survey about stroke history, including whether they had stroke symptoms or had been told they had a stroke.

Nearly 12 percent, or 85 people, said they had. But MRI scans showed 225 people, or 30 percent, had actually suffered a stroke.

People who got it wrong were more likely to have poorer memory or language ability, or have stroke risk factors such as high blood pressure or a history of a heart attacks. Younger people in the study were more likely to get it right.

"However, it is likely that some of the strokes that were not reported were silent strokes," the researchers wrote.

The team said researchers who want to study stroke in older adults need to rely on MRI scans, and not patients, to get accurate information about stroke history.

Review finds conflicts of interest in many cancer studies

12 may 2009--A new analysis finds that a considerable number of clinical cancer studies published in respected medical journals have financial connections to pharmaceutical companies. Published in the June 15, 2009 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that conflicts of interest may cause some researchers to report biased results that are favorable to companies.

Ties between clinical researchers and companies that make medical devices and drugs have become increasingly complex and controversial, particularly as more researchers compete for scarce federal research funds. In addition to using industry money to support their research, some investigators receive consulting fees, own stock and hold positions within companies that profit from selling the very products they are investigating. These conflicts of interest have raised concerns that studies with ties to industry are biased and are not designed to provide a true test of medical therapies. Many medical journals now require researchers to disclose potential conflicts of interest in the articles they submit for publication.

To get sense of the frequency and impact of conflicts of interest in clinical cancer research, Dr. Reshma Jagsi of the University of Michigan and colleagues reviewed cancer studies appearing in eight highly regarded journals in 2006. These journals included the New England Journal of Medicine; JAMA; the Lancet; the Journal of Clinical Oncology; the Journal of the National Cancer Institute; Lancet Oncology; Clinical Cancer Research; and CANCER.

Of the 1,534 cancer studies identified in these journals, 29 percent had conflicts of interest that were apparent from review of published author declarations and authorship lists (including industry funding, consulting fees to authors, co-authorship by industry employees, etc.), and 17 percent declared industry funding. Conflicts of interest were most often found in articles with primary authors from departments in medical oncology (45 percent), those from North America (33 percent), and those with male first and senior authors (37 percent).

According to the authors, randomized clinical trials that assessed patient survival were more likely to report a survival advantage associated with the intervention when a conflict of interest was present. These trials are the foundation by which drugs, technologies, diagnostic tests, etc. get approved for use in the clinic and therefore shape the way oncologists practice medicine.

The findings also show that studies with industry funding were more likely to focus on treatment than studies without industry funding (62 percent vs. 36 percent). They were less likely than studies not declaring industry funding to focus on epidemiology, prevention, risk factors, screening or diagnostic methods (20 percent vs. 47 percent).

This analysis revealed that conflicts of interest exist in a considerable number of clinical cancer research articles published in important journals. The authors noted that "attempts to disentangle the cancer research effort from industry merit further attention, and journals should embrace both rigorous standards of disclosure and heightened scrutiny when conflicts exist."

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Article: "Frequency, nature, effects, and correlates of conflicts of interest in published clinical cancer research." Reshma Jagsi, Nathan Sheets, Aleksandra Jankovic, Amy R. Motomura, Sudha Amarnath, and Peter A. Ubel. CANCER; Published Online: May 11, 2009 (DOI 10.1002/cncr.24306) Print Issue Date: June 15, 2009.

Surgery improves survival for prostate cancer patients younger than 50

For men younger than 50 with prostate cancer, undergoing a radical prostatectomy can greatly increase their chances for long-term survival, according to a new study from Henry Ford Hospital.

12 may 2009--Results from the study done on the National SEER database show that the surgical procedure improves the 5-, 10-, 15- and 20-year survival for younger patients, when compared with other standard treatments such as radiotherapy or watchful waiting.

"When given the choice between surgery, watchful waiting or external beam radiotherapy, patients younger than 50 with moderately and poorly differentiated prostate cancers have better long-term overall and cancer-specific survival when they opt for surgery," says study author Naveen Pokala, M.D., an urologist with Henry Ford Hospital.

Based on findings from the study, Dr. Pokala and co-author Mani Menon, M.D., director of Henry Ford's Vattikuti Urology Institute, strongly recommend retropubic radical prostatectomy – a surgical procedure that removes the entire prostate gland plus some of the tissue around it – as the treatment of choice for prostate cancer patients under the age of 50.

Prostate cancer affects one in six men in the United States during his lifetime, but according to the American Cancer Society only one in 35 will die of it.

Although the majority of all prostate cancer are diagnosed in men older than 65, its prevalence is growing among men younger than 50. In fact, about one in 10,000 men under the age of 40 will be diagnosed this year with prostate cancer.

To determine which treatment option offers the best chance for long-term survival for younger prostate cancer patients, Pokala and Menon studied more than 8,200 men under age 50 with prostate cancer.

Among the study group, 73 percent were white and about 22 percent were black. The mean age was 46, and over 70 percent had moderately and 22 percent had poorly differentiated cancers. Of the patients, 1,065 were managed with no definitive treatment (watchful waiting); 6,614 (79.9 percent) with radical retropubic prostatectomy; and 600 with external beam radiotherapy.

The cancer-specific survival in the NDT group was 78 percent at 16 years, in the radiation group was 63 percent at 17 years; and 94 percent in the radical prostatectomy at 21 years. On a subset analysis the outcome was significantly better after radical prostatectomy in patients with moderately and poorly differentiated prostate cancer.

Overall, the study shows the 5-year, 10-year, 15-year and 20-year overall survival and cancer specific survival is significantly increased in patients who were less than 50 years of age with moderately and poorly differentiated cancers in the surgery group.

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The results were presented in Chicago at the recent American Urological Association's annual meeting.

Age Stereotypes Affect Disease Risk Later in Life

Those who view aging negatively more likely to have cardiovascular event

11 may 2009-- People who have negative views about aging are more likely to have a cardiovascular event later in life, according to research published online Feb. 13 in Psychological Science.

Becca R. Levy, Ph.D., of Yale School of Public Health in New Haven, Conn., and colleagues conducted a study of 386 adults aged 49 years and younger who had experienced no cardiovascular events at baseline and who responded to an age-stereotype predictor. The incidence of cardiovascular events was measured from baseline in 1968 to 2007.

There were 89 cardiovascular events -- including angina attack, congestive heart failure, myocardial infarction, stroke and transient ischemic attack -- during the study period, and cardiovascular events were 1.11 times more common among those who had negative stereotypes about age versus those who did not, while a shift towards a more positive view of aging reduced the risk, the investigators found.

"If an individual's age stereotypes increased in positivity by two standard deviations on the age-stereotype scale, this would lead to an 80 percent reduction in the risk of experiencing a cardiovascular event," the authors write. "The study suggests that age stereotypes internalized earlier in life can have a far-reaching effect on health. In turn, this finding suggests that programs aimed at reducing the negative age stereotypes of younger individuals could benefit their cardiovascular health when they become older."

Abstract
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BEER AND BONE STRENGHT

11 may 2009--A couple of glasses of beer or wine every day is good for your bones, The Sun reported. The Daily Express also covered the story, saying scientists found stronger associations between higher bone mineral density and beer and wine drinkers compared to spirit drinkers. However, the scientists also warned that binge-drinking damages bones and makes them weaker.

This research concluded that there is a stronger association between bone mineral density (BMD) and beer or wine intake relative to drinking spirits, and this indicates that bone health is affected by ingredients other than alcohol. It should not be interpreted to mean that alcohol should be drunk for stronger bones. The results that found an assocation with higher BMD are based on an analysis that only included some of the study participants. In this case, a cautious interpretation of the results is warranted.

Where did the story come from?

The research was carried out by Professor Katherine L Tucker from the Jean Mayer US Department of Agriculture Human Nutrition Research Centre on Aging at Tufts University in Boston, and colleagues from the US, UK and Thailand. The work was supported by several grant bodies, including the United States Department of Agriculture, the National Institutes of Health, and the National Heart, Lung and Blood Institute. The study was published in the peer-reviewed medical journal The American Journal of Clinical Nutrition.

What kind of scientific study was this?

This was an analysis of data from a cohort study, which investigated how different classes of alcoholic drink might affect bone. The researchers say that a previous study in older women found that moderate alcohol intake was associated with increases in bone density, and was therefore protective against fractures caused by osteoporosis. Alcoholism is already known to have negative effects on bone.

The researchers had data from the population-based Framingham Offspring cohort study. This study originally began in 1948 and aimed to look at risk factors for heart disease. In 1971, the adult children of the original participants and their spouses were recruited to take part in further studies, which consisted of a series of questionnaires, an examination and tests every four years. In the fifth and sixth study visits (covering the periods 1991–1995 and 1995–1999), there were 2,919 participants (1,280 men and 1,639 women, aged 29–86 years) with bone mineral density (BMD) measurements available. It is this data that the researchers analysed. The researchers had complete data on the alcohol intake and bone density at three hip sites and the lumbar spine in 1,182 men, 1,289 postmenopausal women and 248 premenopausal women, aged between 29 and 86 years.

The participants usual dietary intake was assessed by a validated 126-item food frequency questionnaire. At the two visits, one in the early 1990s and the other in the late 1990s the participants were asked to complete the questionnaires for their intake throughout the previous year. The average intake from the two questionnaires was used to estimate servings of beer, wine and spirits (liquor) per day. The servings were small by present standards: one serving represented a 356ml glass, bottle, or can of beer, one 118ml serving of wine (red or white) or one 42ml shot of spirits.

A range of other details were collected to allow the researchers to adjust for these in their analyses. These included age, sex, smoking, use of osteoporosis medication, BMI, height, physical activity, and intakes of calcium, vitamin D, magnesium, protein, as well as total energy intakes.

The average age of the participants was 61 years for men, 62 for postmenopausal women, and 48 for premenopausal women. Most people were overweight, and few were smokers.

The researchers also estimated the participants’ average silicon intake from food, beer and wine. They were interested in this because silicon is found in a number of foods, cereals and drink including mineral water and beer. The silicon in beer is found in the form of orthosilicic acid, which is readily absorbed by the body and originates from the husks of barley. The silicon intake was calculated from the dietary questionnaires data by taking average values (mg of silicon) for each food item and adding these together to obtain total silicon intake per person per day.

What were the results of the study?

The researchers reported that the men in their study were predominantly beer drinkers, whereas women were predominantly wine drinkers.

Men who consumed one to two drinks a day of total alcohol or beer had greater bone density at the hip (4.5%) than the non-drinkers (3.4%). Postmenopausal women who drank more than two drinks a day of total alcohol or wine had significantly greater bone density at the hip and spine (8.3%) than non-alcohol drinkers (5.0%).

Men who drank more than two drinks a day of spirits had significantly lower bone density at the hip (3.0%) than those who drank one to two drinks a day of spirits (5.2%).

After adjusting for silicon intake, all intergroup differences for beer were no longer significant. The differences for other alcohol sources remained significant.

The researchers note that power was low, meaning that the study was too small to analyse the premenopausal women separately, and the associations were not significant.

What interpretations did the researchers draw from these results?

The researchers say that this is the first study to look at bone density and intakes of different classes of alcoholic beverages in men and post- and premenopausal women.

They say that the results support earlier observations that moderate alcohol intake may protect BMD in postmenopausal women and older men. The benefits are most apparent from beer and wine, which suggests that factors in conjunction with ethanol may be having the protective effects.

They say that “silicon appears to mediate the association of beer, but not that of wine or liquor, with bone density” and suggest areas that could benefit from further investigation.

The interpretation of this study and any implications for those who drink alcohol are complex. There are anomalies in the findings, which appear to counter the view that alcohol is “good for bones”. For example:

• The effect appears to differ between men and women.
• The effect seems to be different for women before and after the menopause.
• The effect varies according to different types of alcohol.
• Part of the effect can be removed if a statistical adjustment for silicon content of food and drink is made.
• While there are some significant differences between the groups (such as between those men drinking two or more glasses of alcohol compared to no alcohol), when the data was analysed for the trend (i.e. whether increasing alcohol consumption overall is associated with increasing bone density) many of these overall trends are no longer significant. This means that the relationship is probably not a simple linear one between alcohol and bone density.

Although it is possible to speculate about the reasons behind these associations, it is better in principle to interpret these results with caution. This is usually the case with studies like this, which demonstrate a mixture of significant and non-significant effects when the data is cut into small sub groups. Caution is particularly important when some of these sub groups show a benefit for alcohol in terms of bone density (beer in men) and some show a harm (spirits for men, but not women).

Links to the headlines

Booze aid for our bones. The Sun, March 4 2009

Sip beer for stout bones. The Mirror, March 4 2009

Beer is a tonic for the bones. Daily Express, March 4 2009

Links to the science

Tucker KL, Jugdaohsingh R, Powell JP, et al. Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr (February 25, 2009)

STATINS CUTS RISK OF DVT

11 may 2009--Taking a common heart drug “halves the risk of death from DVT,” reports the Daily Express. The newspaper says that a commonly prescribed statin pill “slashes the risk of the killer condition deep vein thrombosis by more than half.”

These results come from research into use cholesterol-lowering statin drug by apparently healthy people. In this publication researchers focused on the role the drug plays in preventing venous thromboembolism (the development of clots in the veins of the legs or lungs). DVT can be caused by sitting still during long-haul air travel or being confined to bed for long periods.

The well-conducted study provides good evidence that the statin can reduce risk of DVT in apparently healthy people, and that this effect is not simply a result of statins reducing the chance of heart-related illness, which can raise the risk of DVT. The researchers imply that this research offers a new reason for prescribing the drug.

However, the participants in this study had to meet a number of criteria, and although apparently healthy, they were all at higher risk of a cardiovascular event than the general population. The results may not apply to the wider population, and more research will be needed before statins can be widely used to prevent DVT as suggested.

Where did the story come from? This research was conducted by Dr Robert Glynn and colleagues from Brigham and Women’s Hospital in Boston, Universidade Federal de Sao Paulo, McGill University Health Centre in Montreal, and other academic and medical institutions in Denmark, Argentina and Scotland.

The research was funded by the AstraZeneca pharmaceutical company, and by a grant from the National Institutes on Aging. It was published in the peer-reviewed medical journal, the New England Journal of Medicine.

What kind of scientific study was this? This study was a large randomised controlled trial that reported on the effects of statin use on occurrence of venous thromboembolism (deep vein thrombosis and pulmonary embolism). Apparently healthy individuals were randomly allocated to receive rosuvastatin (20mg daily) or a placebo.

This study used data from the large ‘Jupiter trial’, which was originally set up to assess the role of rosuvastatin for primary prevention of cardiovascular events in people with higher C-reactive protein (CRP) levels. CRP is a protein that is produced in reaction to inflammatory processes in the body, and it is thought to be a marker of increased risk of diabetes and cardiovascular diseases. The occurrence of venous thromboembolism was a secondary outcome from this initial Jupiter study.

Although statins such as rosuvastatin are used for managing cholesterol levels, it is also thought that they reduce inflammation, with observational studies showing a 22% to 50% cut in risk. This study is one of the first randomised studies to report on any possible anti-inflammatory effects of statins.

A total of 17,802 people were randomised within this study. To be eligible for inclusion, they had to meet the following criteria:

• Be aged at least 50 years for males or 60 years for females.
• Have no known cardiovascular diseases at an initial screening visit.
• Have a low-density lipoprotein (LDL) cholesterol level of less than 3.4 mmol/L, and a high-sensitivity C-reactive protein (CRP) level of 2.0 mg/L or more.

Between March 2003 and December 2006, participants were randomised into either an active group, receiving a daily 20mg dose of rosuvastatin, or a placebo. They were followed-up for an average of 60 months after randomisation, with regular visits to the study team for interim interviews that assessed the occurrence of outcomes.

Any reported venous thromboembolism was confirmed using a venous ultrasonogram or venogram for DVT. For confirmation of pulmonary embolism, angiograms, computed tomographic scans or ventilation–perfusion scans were used.

The Jupiter trial on rosuvastatin was stopped in March 2008 because evidence of efficacy of the statin’s effectiveness was convincing. Events up to this date were included in the analysis. To account for the fact that thromboembolism often occurs around the time of cardiovascular events, the researchers performed separate analyses for venous thromboembolism and for primary cardiovascular events.

What were the results of the study? A pulmonary embolism or DVT occurred in 94 participants, with 34 in the statin group and 60 in the placebo group. Rosuvastatin reduced the combined risk of these outcomes by 43% (HR 0.57, 95% CI 0.37 to 0.86). There was a similar-sized effect of statin on prevention of either a primary cardiovascular event or a venous thromboembolism (HR 0.56, 95% CI 0.47 to 0.68).

Venous thromboembolism was more common in those people over 70 years with a high BMI and large waist circumference. Cholesterol levels at time of entry to the study (baseline) did not have any effect on the efficacy of the drug. The researchers do not discuss the side effects of statin use in this publication.

What interpretations did the researchers draw from these results? The researchers report that 20mg of rosuvastatin a day reduces the risk of symptomatic venous thromboembolism in apparently healthy people. They say that this reduction in risk appears to be an independent benefit of statin use, in that it does not depend on the reduction in risk of heart attacks or strokes.

They go on to say that as a result of this newly observed benefit of statins, the research goal should be widened from preventing arterial thrombosis to preventing venous thromboembolism and death too.

What does the NHS Knowledge Service make of this study? This randomised control trial found that daily rosuvastatin reduces the risk of venous thromboembolism: the study was large and well-conducted and offers robust evidence for the successful treatment of DVT with this drug.

This study only assessed the role of statin treatment in outcomes of symptomatic venous thromboembolism. The researchers say that because asymptomatic venous thromboembolism is common too, the study may have underestimated the beneficial effects of the drug by not assessing this outcome as well.

It should be noted that the selection of participants who took part in this study make it harder to apply the findings to the general population. In particular:

• Only people with higher levels of CRP were entered into this study, meaning that although none of them had yet had a cardiovascular event, they were at a higher risk of having one than the general population.
• In both the rosuvastatin and placebo groups, 37.6% of the subjects were obese, with a BMI of more than 30.
• 41.7% of the participants had metabolic syndrome, another marker of increased risk.

It should also be noted that despite higher-than-average risk of venous thromboembolism, the absolute number of events in this group of people was low, with only 94 episodes among all the 17,802 participants.

In general, this large randomised trial confirms previous findings from observational studies, but also raises further questions about who exactly should be offered treatment with these drugs. Further analysis of the subgroups results from this study, as well as repeated trial in groups with normal CRP levels will be required before new indications for statin use can be confirmed.

Links to the headlines

Heart drug 'halves the risk of death from DVT'. Daily Express, March 30 2009

Cholesterol busting drugs 'can prevent fatal blood clots in healthy people'. The Daily Telegraph, March 30 2009

Common drug could cut risk of fatal blood clots. The Times, March 30 2009

Links to the science

Glynn RJ, Danielson E, Fonseca FAH et al. A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism. NEJM 2009 [Advanced online
publication 30 March]

FACE CREAM REDUCES WRINKLES

11 may 2009--Scientists say that, “a skin cream sold on the high street has been clinically proven to reduce fine wrinkles and improve the appearance of weathered skin,” The Times

reported. It said that a trial of 60 volunteers with signs of sun-damaged skin, found that the cream from the chemist Boots, helped to reduce signs of ageing. The newspaper reported that 70% of people who used the cream for a year had significantly fewer wrinkles compared with volunteers using a placebo. This popular story was covered by most UK national newspapers.

This new study was a double-blind randomised controlled trail and has been welcomed for "raising the bar" (The Guardian) on the kinds of tests cosmetic companies should do before making claims for their products. Although the study has a few limitations in how it was reported, and there was no significant difference in benefit at six months between the test group and a group given a placebo, there is a clear trend towards benefit. If the cream were to be regulated as a medicine, the next step would be larger trials that confirmed the affect.

Where did the story come from?

The research was carried out by Dr Rachel Watson and colleagues from the Dermatological Sciences Research Group at the University of Manchester. One of the authors is employed by Alliance Boots Ltd, the manufacturer of the cream. Sources of funding are not reported. The study was published in the peer-reviewed British Journal of Dermatology.

What kind of scientific study was this?

The researchers say that very few over-the-counter cosmetic ‘anti-aging’ products have been subjected to rigorous testing. This was an investigation of one such product involving a double-blind randomised controlled trial and an ‘in vivo’ patch testing study. Both parts of the study tested the same product: No.7 Protect and Perfect Intense Beauty Serum manufactured by Alliance Boots.

This product consists of a water in silicone emulsion. It contains glycerine and other emollients, plus a number of ‘anti-ageing’ ingredients. These ‘anti-ageing’ ingredients include extracts from plants (Panax ginseng, Morus alba, Lupinus alba, Medicago sativa), as well as small pieces of protein called peptides (palmitoyl oligopeptide, palmitoyl tetrapeptide-7) as well as vitamin derivatives (sodium ascorbyl phosphate, tocopherol and retinyl palmitate). Retinyl palmitate (a retinoid) is thought to be the active ingredient and is a synthetic ester derived from vitamin A. More potent, prescription-only, retinoids are used to treat mild to moderate acne. The researchers used one of these, all-trans retinoic acids (ATRA) as a comparison (a positive control), in the ‘in vivo’ patch test study. ATRA is known to cause the skin to produce fibrillin-1, which itself predicts the formation of collagen. More collagen should result in skin rejuvenation.

The researchers recruited 10 people (four men and six women, aged 61 to 76 years) whose skin that had been photoaged (sun damaged). Each person underwent a patch test then had small amounts (20 microlitres) of the No.7 product or a control ‘vehicle’ cream applied to separate small areas (6mm in diameter) of clean, photoaged skin on their forearms. The areas were then covered over with dressings. Similarly sized areas of skin had no cream applied but were covered over to act as untreated controls. The control and the test product were applied to skin on the first, fourth, and eight days of the test. In addition, an all-trans retinoic acid (ATRA) cream (Retin-A cream produced by Janssen-Cilag Ltd. containing 0.025% retinoic acid) was applied to an area of untreated skin on the eighth day and left on the skin for four days. The vehicle cream represented a negative control, while the ATRA cream represented a positive control.

Twelve days after the test began, skin samples (biopsies) were taken from the four forearm areas (the No.7 test product area, control cream treated area untreated area, and the ATRA positive control area). The researchers used a standard technique using antibodies to look at how much of the fibrillin protein was present in thin slices from these skin samples, scoring the levels from zero (lowest) to four (highest).

The randomised-controlled trial involved 60 recruits with photo-aged skin (11 men and 49 women, aged 45 to 80 years). In it, the researchers compared the No.7 Protect and Perfect Intense Beauty Serum and a control (vehicle) cream without the ‘anti-ageing’ ingredients.

Participants were randomly assigned to receive the test or control cream, each in identical packaging so that neither the volunteers nor the researchers knew which they were receiving. They applied the cream to their face and the backs of their hands, wrists and forearms every evening for six months.

The participant’s faces and the backs of their hands were examined by researchers at the start of the study and at one, three and six months. The researchers looked for fine lines and wrinkles, areas of abnormal colouration, overall level of signs of ageing of the skin by the sun and roughness of the skin to the touch. All four of these aspects of the skin were rated from zero to eight. Zero indicated the least evidence of photoageing or fine lines and wrinkles, no areas of abnormal pigmentation or totally smooth skin. Eight indicated the most severe photoageing or fine lines or wrinkles, severe abnormal pigmentation or very roughened skin. Scores for these four aspects of skin appearance were compared in the test and control groups.

Twenty-eight of the volunteers (13 from the control and 15 from the test group) agreed to provide skin biopsies from their wrist at the start and end of the study. The researchers looked for the levels of fibrillin in these tissue samples. All volunteers were monitored for serious side effects of the treatment during the treatment period and for 28 days afterwards.

After the six-month initial trial period, all volunteers were offered and used the No.7 product for a further six months. The researchers compared 12-month results from the treated volunteers with what would be expected in the control group by using statistical modelling based on the vehicle response at six months to predict the expected outcome at 12 months.

What were the results of the study?

The patch testing showed that the skin treated with the test cream contained more fibrillin than the untreated control skin. Skin treated with the all-trans retinoic acid cream (positive control) had similarly increased levels of fibrillin but treating the skin with vehicle cream alone did not significantly affect the level of this protein.

On a scale of zero (lowest) to four (highest), the average level of fibrillin in the skin was rated as 1.3 for the untreated control skin, 1.7 for the vehicle cream, 2.5 for the all-trans retinoic acid cream, and 2.6 for the test product.

After six months, 43% of people in the randomised-controlled trial using the test product, showed an improvement in facial wrinkles compared to the start of the study, this was a statistically significant increase. After six months, 22% of those using the control cream had improvements in facial wrinkles compared to the start of the study, but this was not statistically significant. The difference in the proportion of people with improved appearance of wrinkles between the tested and the control cream (21% or one in five) was also not statistically significant.

When the researchers gave all participants the test cream, they found that at 12 months 70% of the people showed an improvement in facial wrinkles compared to the start of the study. Statistical modelling predicted that 33% of people would have shown improvement in their wrinkles if they continued to use the control (vehicle) cream for 12 months. The proportion of participants who showed improvement in this model (37%) was statistically significant.

The improvement in the test group was described as “clinically significant”. Skin samples showed that wrist skin treated with the test product for six months contained more fibrillin than control (vehicle) treated wrist skin.

The researchers did not observe any other benefits of the test product over the control. For example, there were no improvements in the amount of abnormal colouration (mottled dyspigmentation) of the skin and both the test and control products produced similar improvements in skin roughness from the start of the study.

What interpretations did the researchers draw from these results?

The researchers say that they have shown “for the first time that a commercially available over-the-counter anti-ageing product improves the appearance of facial wrinkles when used in the long-term”. They say that the improvement is associated with “restoration of fibrillin-1” and that this further supports the use of fibrillin-1 as a marker for assessing the efficacy of similar products.

This randomised-controlled trial used double blinding to reduce the risk of bias for the six-month outcomes and a validated scale to provide as objective a measure of the actual skin appearance as possible. There are aspects of the reporting and the statistical analysis in this study of note when:

• The characteristics of the treated and control groups before the study began are not described. Even in randomised trials, there can be important differences between groups that can sometimes partly explain the results.
• The results and significance between the cream and control groups at six months are not fully reported. If these had been provided, it would be possible to judge how close to a significant result the six-month trend came.
• The assumptions underlying the extrapolation of the control group results to 12-months are not reported.
• The dropout rates are not reported, nor is any measure of compliance with the cream between the groups.
• The study was small, therefore limiting its ability to detect a true difference in outcomes.
• Any minor adverse effects, such as skin redness or irritation, common with the more potent topical retinoids, are not reported.

As all participants knew that they were receiving the test cream in the ‘open’ part of this trial from six months to 12 months, this has effectively compromised the benefits of blinding. Although there are understandable reasons why this was done, it remains to be seen what benefits there may be if a larger trial was conducted for the full 12 months.

Links to the headlines

Is a scientist's face proof that a £20 skin cream really gets rid of wrinkles? The Independent, April 29 2009

Boots anti-wrinkle cream actually works, say researchers. The Guardian, April 29 2009

High St skin cream really does reduce the signs of ageing. The Times, April 29 2009

'Proof' face creams beat wrinkles. BBC News, April 29 2009

Protect and Perfect: anti-ageing face cream 'first proven to reduce wrinkles'. The Daily Telegraph, April 29 2009

The £19 anti-wrinkle cream set to cause a stampede at Boots after scientists claim it DOES actually work. Daily Mail, April 29 2009

Wonder cream does banish wrinkles, say scientists. Daily Express, April 29 2009

£20 Boots gel beats wrinkles. The Sun, April 29 2009

Cream does cut wrinkles say experts. Daily Mirror, April 29 2009

Links to the science

Watson REB, Ogden S, Cotterell LF, et al. A cosmetic 'anti-ageing' product improves photoaged skin: a double-blind, randomized controlled trial. British Journal of Dermatology 2009; Published Online 28 Apr

WINE DRINKERS LIVE LONGER


11 may 2009--Half a glass of wine a day can add five years to your life” The Daily Telegraph has said, claiming that new research shows that that light, long-term consumption boosted longevity, ‘with the biggest increase caused by wine’.

The study behind this article ran from 1960 to 2000, and enrolled 1373 men born between 1900 and 1920. The results suggest that men consuming an average of 8g of alcohol from wine per day (equivalent to about half a small glass) may live about 5 years longer than those who don’t consume alcohol.

This is not a precise estimate, and the results suggest the real difference could lie anywhere between 1.6 and 7.7 years. This researchers took care to consider other factors that may be linked to both wine consumption and mortality, i.e. factors that mean people consuming wine are systematically different from those who do not. The researchers took into account the obvious factors of smoking habits and social/ economic class but others important factors were not investigated. This justifies the researchers’ cautious conclusion that more studies are needed to verify their results.

Where did the story come from?

The study was undertaken by Drs Streppel and colleagues from the National Institute for Public Health and the Environment in Bilthoven and the Division of Human Nutrition at Wageningen University, both in the Netherlands.

It was published in the peer-reviewed Journal of Epidemiology and Community Health, and partially funded by the former Inspectorate for Health Protection and Veterinary Public Health (at present integrated in the Food and Consumer Product Safety Authority).

What kind of scientific study was this?

This was a cohort study looking at male alcohol consumption and rates of mortality among 1373 Dutch men within a 40 year period.

This Zutphen Study (named after a town in eastern Holland) began in 1960, when a random sample of men who were born between 1900 and 1920 and living in Zutphen for at least 5 years were drawn from the town.

The initial sample was 1088 men, although only 878 (81%) of them participated in the study. They were initially interviewed in 1960, and then again in 1965, 1970, 1985, 1990, 1995 and 2000. By 1985 there were only 554 survivors, so the researchers increased their sample size by recruiting an additional random sample of men (also born between 1900 and 1920).

Of the 1266 men invited in 1985, 939 men participated. In total 1817 there were participants, although researchers excluded those men who did not take part in dietary and physical examinations at each round, leaving 1373 in their analyses.

This second group of men were assessed four times; upon joining the study in 1985 and then again in 1990, 1995 and 2000. During the assessments prior to 1985 all participants were asked about alcohol and food consumption in the 12 months preceding the interview, while alcohol intake in the previous month was assessed for interviews after 1985.

Food consumption tables were used to determine the daily intake of alcohol, energy and other nutrients. For those participants who joined the study in 1985, their missing consumption data were imputed, i.e. modelled to fill in the gaps.

The link between alcohol consumption (beer, wine or spirits) and mortality was determined by categorising men by alcohol consumption levels of 0g, 0-20g and more than 20g per day. Many factors (confounders) may be linked to both alcohol consumption and mortality outcomes. The researchers measured some of these potential confounders including;

• smoking status (never or long-term ex-smokers, recent ex-smokers, current smokers)
• length of any smoking,
• BMI,
• health history including any history of heart attack, stroke, diabetes or cancer,
• a measure of socioeconomic status (manual workers, non-manual workers, small business owners and professionals) which was determined by the participants occupation at baseline.

They also considered dietary variables including vegetable, fruit and fish consumption as well as saturated fats.

Researchers were interested in assessing the link between long-term intake of alcohol and cardiovascular and all-cause mortality, according to each type of alcoholic beverages consumed. The life expectancy of the men at baseline (average age 50 years) was compared across consumption types and categories. Death certificates were used to determine official causes of death.

What were the results of the study?

During the 40 years of follow up, 82% (1130 of 1373) of the men died. In total 628 deaths were due to cardiovascular disease; 348 from coronary heart disease and 139 from cerebrovascular events.

Numbers using alcohol increased from 45% in 1960 to 86% in 2000, and from an average of 8g/day to 14g/day (with a peak of 18g/day in 1985). Long-term use of alcohol was linked to a reduced risk of death; compared to men who did not drink, those drinking between 0-20g/day had a 57% lower cerebrovascular mortality risk, a 30% lower risk of death due to cardiovascular disease (CVD) and a 25% reduced risk of death due to any cause.

When assessing alcohol by type, wine had the strongest effect, with those consuming an average of 0-20g of wine per day having a 39% reduced risk of coronary heart disease (CHD), a 32% reduced risk of CVD and a 27% reduced risk of death from any cause. Conversely, beer or spirits did not reduce mortality risk. This effect was similar across all socioeconomic categories.

Overall, men consuming an average of 6g/day of alcohol (from beer, wine or spirits) could expect to live 2.3 years longer from age 50 than those who did not consume alcohol. When limiting the calculation to wine drinkers, those who drank an average of 8g alcohol/day from wine (less than half a glass per day) lived 4.7 years longer than those who didn’t use alcohol.

What interpretations did the researchers draw from these results?

The researchers conclude that long-term light alcohol intake reduces cerebrovascular, total cardiovascular disease and all-cause mortality.

The authors have raised several weaknesses of their study:

• Firstly, they were unable to investigate the effects of drinking frequency, which is important because some studies suggest that frequency of alcohol consumption is linked to a reduced risk of coronary heart disease independent of the amount consumed.
• The estimates of missing data for those participants who joined the study in 1985 may have led to some biases. The researchers considered this a good approach as consumption around the time these men joined was higher than in the preceding years. They say that they repeated their analyses in only the men who had been in the study since 1960, and found their results were similar to those from analysing the whole sample.
• Their finding that the highest exposure to alcohol did not lead to increased mortality is in contrast to other studies. The researchers explain this by saying that their highest intake category was ‘relatively low’ (29g/day), and this may explain why there was no link with this category and death.

The researchers have adjusted for obvious confounders – smoking and socioeconomic status – and conclude that the association found between wine consumption and mortality is not explained by these factors.

It is important to note that although those drinking an average of 8g alcohol from wine per day lived about 5 years longer than those who didn’t drink alcohol, this was not a very precise estimate: the researchers were confident the difference was somewhere in the range of 1.6 to 7.7 years.

The conclusions from cohort studies such as this are sensitive to the consideration of other factors that may potentially be linked to both consumption and mortality. Although researchers took into account the major factors of smoking and socioeconomic status, there may be other differences between wine drinkers and teetotallers that are not captured in the analysis. Physical activity, which is linked to mortality, may be one such factor.

As the researchers cautiously conclude, ‘more studies are needed to draw conclusions on the strength of the association between wine consumption and mortality’.

Links to the headlines

Wine may help men outlive teetotallers. The Guardian, April 30 2009

Half a glass of wine a day can add five years to your life. The Daily Telegraph, April 30 2009

Good health! Daily Mirror, April 30 2009

Links to the science

Streppel MT, Ecke MC, Boshuizen HC et al. Long-term wine consumption is related tocardiovascular mortality and life expectancy independently of moderate alcohol intake: theZutphen Study. J Epidemiology and Community Health, April 30 2009 [Advanced online publication]

PAD Frequently Undiagnosed in Heart Disease Patients

Condition is overlooked in up to 15 percent of patients; systematic screening recommended

10 may 2009-- As many as one in six patients with coronary artery disease (CAD) may have overlooked peripheral arterial disease (PAD) despite specialist cardiovascular care, according to a study published in the May issue of Catheterization & Cardiovascular Interventions.

Issam D. Moussa, M.D., of the New York Presbyterian Hospital/Weill Cornell Medical Center in New York City, and colleagues assessed 800 patients without known PAD who were referred for coronary angiography.

Overall, the researchers found that the prevalence of overlooked PAD was 15 percent, and that the prevalence was highest among subjects over age 70 years and women (25.2 and 23.3 percent, respectively). They also found that subjects with multi-vessel CAD were twice as likely to have previously unrecognized PAD as those with single-vessel CAD.

"These findings extend the results of previous research and not only suggest a greater burden of atherosclerotic disease and later presentation, but also provide a possible explanation for the worse outcome of patients with concomitant CAD and PAD compared with those without PAD," the authors write. "Therefore, making a diagnosis of PAD in a patient with CAD should prompt the clinician to be more aggressive with risk factor intervention, foot protection, and a high clinical index of suspicion for progressive PAD symptoms. These patients must be viewed as exceptionally 'high risk.' Systematic, ankle-brachial index-based, PAD screening programs should be implemented in all patients with CAD."

This study was supported by Sanofi-Synthelabo.

Abstract
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X-rays help predict permanent bone damage from bisphosphonates

CHICAGO , 10 may 2009- Breast cancer patients, individuals at risk for osteoporosis and those undergoing certain types of bone cancer therapies often take drugs containing bisphosphonates. These drugs have been found to place people at risk for developing osteonecrosis of the jaws (a rotting of the jaw bones). Dentists, as well as oncologists, are now using X-rays to detect "ghost sockets" in patients that take these drugs and when these sockets are found, it signals that the jawbone is not healing the right way. Early detection of these ghost sockets can help the patient avoid permanent damage to their jawbone, according to an article in the March/April 2009 issue of General Dentistry, the Academy of General Dentistry's (AGD) clinical, peer-reviewed journal.

A ghost socket occurs when the jawbone is not healing and repairing itself the right way. "The good news is that even though these ghost sockets may occur, by using radiographic techniques we can see that the soft tissue above these sockets can still heal," according to Kishore Shetty, DDS, MS, MRCS, lead author of the report. Dr. Shetty states these findings are important news to learn about because early prevention and detection can halt permanent damage from happening to a patient's jawbone.

In 2006, about 191 million prescriptions of oral bisphosphonates worldwide were written. The National Osteoporosis Foundation estimates that nearly 44 million people in the United States are at risk for developing osteoporosis. Currently, approximately 10 million Americans suffer from the disease.

Bisphosphonates are a family of drugs used to prevent and treat osteoporosis, multiple myeloma, Paget's disease (bone cancers), and bone metastasis from other cancers. These drugs can bond to bone surfaces and prevent osteoclasts (cells that break down bone) from doing their job. Other cells are still working trying to form bone, but it may turn out to be less healthy bone leading to the ghost-like appearance on X-rays.

"Healthy bones can easily regenerate," says Dr. Shetty. "But, because jawbones have rapid cell turnover, they can fail to heal properly in patients taking any of the bisphosphonate drugs. It's very important for patients to know about complications from dental surgery or extractions. Since these drugs linger in the bone indefinitely, they may upset the cell balance in how the jaws regenerate and remove unhealthy bone."

According to AGD spokesperson Carolyn Taggart-Burns, DDS, FAGD, patients who are taking bisphosphonates should inform their dentist to prevent complications from dental surgical procedures.

"Widespread use of bisphosphonates to prevent or treat early osteoporosis in relatively young women and the likelihood of long-term use is a cause for concern," says Dr. Taggart-Burns.

Drs. Shetty and Taggart-Burns agree that, "how bisphosphonates interfere with healing after dental surgery is still unclear and further research will be needed. It is imperative that the public understands there is no present treatment or cure for this problem."

Study: Prostate cancer vaccine extends survival

CHICAGO, 10 may 2009-- — An experimental treatment added four months to the lives of men with advanced prostate cancer in a study that tested an entirely new approach to fighting the disease, doctors reported today.

Dendreon Corp.’s Provenge vaccine trains the immune system to fight tumors. It’s called a “vaccine” even though it treats disease rather than prevents it.

Doctors have been trying to develop such a therapy for decades, and this is the first to meet a preset goal for improving survival in late-stage testing.

“There have been a lot of false starts, but this is a real start,” said Dr. Paul Schellhammer, a urologist at Eastern Virginia Medical School in Norfolk, Va., who led the study. Results were reported today at an American Urological Association conference in Chicago.

Seattle-based Dendreon paid for the study, and Schellhammer owns stock in the company. Dendreon shares fell sharply, and then trading was halted leading up to the release of the data. Shares fell $9.74, or 45.2%, to $11.81. The reason was not immediately clear.

Four months may not sound like a lot, but it is longer than the three months afforded by Taxotere, the only chemotherapy approved for men in this situation.

Doctors hope for even greater benefit if they give the drug earlier in the course of the disease. Dendreon would give no cost estimate for Provenge, but other such biotech drugs cost several thousand dollars a month.

It remains to be seen if side effects will keep Provenge from winning federal Food and Drug Administration approval. Two years ago, the FDA went against its advisers and delayed a decision, asking for more proof of safety and effectiveness.

The new study involved 521 men whose cancer had spread and wasn’t responding to standard hormone treatments. Two-thirds were given Provenge, a treatment that is customized for each patient.

Doctors collect special blood cells from each patient that help the immune system recognize cancer as a threat. They are mixed with a protein found on most prostate cancer cells and another substance to rev up the immune system. The resulting “vaccine” is given back to the patient as three infusions two weeks apart.
The other one-third of men in the study had a dummy infusion.

Median survival was 26 months in men given Provenge and 22 months in the others. Three-year survival rates were 32% for the Provenge group and 23% for the others — a 38% improvement.

Strokes and other brain-related problems were no more common with Provenge — a worry raised by earlier studies. However, four men given Provenge suffered lung clots, though none were fatal. High blood pressure was twice as common with Provenge. Overall, the rate of serious side effects was the same in each group.

Improving survival “is the gold standard” for any treatment, and Provenge appears to do that, said Dr. Ira Sharlip, a urologist from the University of California in San Francisco and a spokesman for the urological association.

Dr. Otis Brawley, the American Cancer Society’s chief medical officer, said the FDA had been right to ask for more study. Seeing the new results, he said, “I would vote for approval” as long as it didn’t harm men’s quality of life.

One patient said it did not hurt his. Thomas Robbins, 74, of Forest City, N.C., was diagnosed in 2002 with prostate cancer that was growing despite hormone treatment.

“They wanted to give me chemo,” but he feared its side effects and enrolled in the Provenge study instead. He learned afterward that he had been one of those given the vaccine.

“Did it help me? I can’t 100% guarantee, but I think it did,” he said.

Advocacy groups cheered the results. Scott Riccio, founder of Accelerate Progress, called them “compelling.”

“For the first time, we have real clinical validation that cancer can be fought by stimulating the body’s immune system,” he said in a statement. “Hundreds of thousands of men fighting prostate cancer will now have real hope that a safe and effective new option will be available to them in their fight for life.”

Thomas Farrington, a prostate cancer survivor and founder of the Prostate Health Education Network, said: “Prostate cancer patients finally have hope for a better life. We are in desperate need of groundbreaking new treatments like Provenge.”

Prostate cancer is the most common non-skin cancer in American men. An estimated 186,000 new cases and 28,660 deaths from it occurred last year.